Interventions for Tuberculosis Control and Elimination 2002

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and 0.5 mg/L in agar. 21-23 Rifampicin is active against a wide range of
micro-organisms including M. leprae, S. aureus, N. meningitidis, and L. pneumophila.
Rifampicin, like all naphthalenic ansamycins (the class to which
rifampicin belongs), is a specific inhibitor of DNA-dependent RNA polymerase.
175
Rifampicin acts by interfering with the synthesis of mRNA by binding
to the RNA polymerase. 176 Mycobacteria develop resistance to
rifampicin by mutations in a defined region for the RNA polymerase subunit
β. Mutations in the rpoB gene of M. tuberculosis are responsible for
most of the resistance. 177 Mutations have been found in more than 97%
of resistant isolates. 178,179
The maximum proportion of rifampicin-resistant mutants able to grow
during rifampicin monotherapy of an isoniazid-susceptible strain is estimated
to be approximately 1 in 10 8 . 53
Pharmacokinetics. After oral administration of rifampicin on an empty
stomach, the absorption is rapid and practically complete. 180 With a dose
of 8.1 (± 0.7) mg/kg body weight, a peak level of 6.3 (± 0.5) mg/L is
achieved 3.2 hours after oral administration. After oral intake of 600 mg
27
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Figure 12. Chemical structure of rifampicin, isolated and semi-synthesized by
Maggi and collaborators in 1966. 174